External Ophthalmoplegia, C10ORF2 and mtDNA Mutations

Background and History: 

This disorder of eye movement was first described by an ophthalmologist, Albrecht Von Graefe, in 1868.  A number of genetic disorders are associated with difficulties in eye movement, known as external ophthalmoplegia. The type described here has primarily ocular symptoms but systemic disease occurs as well.

Clinical Correlations: 

Patients may notice droopy eyelids (ptosis) and difficulty moving the eyes as early as 20 years of life but onset is usually not until midlife or later.  About half of patients notice some general muscle weakness and about a quarter may have heart rhythm problems.  Some patients have parkinsonism-like symptoms such as unsteadiness, stiffness and difficulty moving rapidly.  Some also report difficulty swallowing and speaking.  Mental changes such as depression and bipolar disorder has been reported in a few families.


This is an autosomal dominant disorder caused by a gene mutation located on a chromosome as well as changes in the DNA of the mitochondria (power generators of cells).  The condition is transmitted directly from an affected parent in a vertical pattern.

Diagnosis and Prognosis: 

Ophthalmologists and neurologists are usually the ones who diagnose this disorder.  There are multiple types caused by different mutations and the prognosis depends on which mutation is responsible.  The prognosis is generally good with no evidence that lifespan is shortened.

There is no treatment for the eye movement problems but the droopy eyelids can be elevated surgically.

Additional Information
Autosomal dominant